Expiratory Activity Research Articles

Electrophysiological properties of laryngeal motoneurones in rats submitted to chronic intermittent hypoxia.

The respiratory control of the glottis by laryngeal motoneurones is characterized by inspiratory abduction and post-inspiratory adduction causing decreases and increases in upper airway resistance, respectively. Chronic intermittent hypoxia (CIH), an important component of obstructive sleep apnoea, exaggerated glottal abduction (before inspiration), associated with active expiration and decreased glottal adduction during post-inspiration. CIH increased the inspiratory and decreased the post-inspiratory laryngeal motoneurone activities, which is not associated to changes in their intrinsic electrophysiological properties. We conclude that the changes in the respiratory network after CIH seem to be an adaptive process required for an appropriated pulmonary ventilation and control of upper airway resistance under intermittent episodes of hypoxia. To keep an appropriate airflow to and from the lungs under physiological conditions a precise neural co-ordination of the upper airway resistance by laryngeal motoneurones in the nucleus ambiguus is essential. Chronic intermittent hypoxia (CIH), an important component of obstructive sleep apnoea, may alter these fine mechanisms. Here, using nerve and whole cell patch clamp recordings in in situ preparations of rats we investigated the effects of CIH on the respiratory control of the upper airway resistance, on the electrophysiological properties of laryngeal motoneurones in the nucleus ambiguus, and the role of carotid body (CB) afferents to the brainstem on the underlying mechanisms of these effects. CIH rats exhibited longer pre-inspiratory and lower post-inspiratory superior laryngeal nerve activities than control rats. These changes produced exaggerated glottal abduction (before inspiration) and decreased glottal adduction during post-inspiration, indicating a reduction of upper airway resistance during these respiratory phases after CIH. CB denervation abolished these changes produced by CIH. Regarding choline acetyltransferase positive-laryngeal motoneurones, CIH increased the firing frequency of inspiratory and decreased the firing frequency of post-inspiratory laryngeal motoneurones, without changes in their intrinsic electrophysiological properties. These data show that the effects of CIH on the upper airway resistance and laryngeal motoneurones activities are driven by the integrity of CB, which afferents induce changes in the central respiratory generators in the brainstem. These neural changes in the respiratory network seem to be an adaptive process required for an appropriated pulmonary ventilation and control of upper airway resistance under intermittent episodes of hypoxia.

Integral activity of intrapulmonary source of mechanical energy in healthy subjects and in patients with obstructive lung diseases

Two functional levels of mechanical energy intrapulmonary source have been viewed in this article for the first time. The first level is located into the perialveolar space. This level provides inspiratory and expiratory activity of the lungs together with respiratory muscles. Due to this, the inspiratory alveolar pressure is lower than the intrapleural pressure and the expiratory alveolar pressure is higher than the intrapleural pressure. This is deter mined by work of breathing measured as negative elastic hysteresis area and allows overcoming some nonelastic resistance of the lungs. The lung activity on overcoming the elastic resistance is estimated by multiplying the total work of breathing by a functional coefficient of lung elasticity (FCLE). The latter is calculated by dividing the total lung compliance by the dynamic lung compliance and reflects change in the elastic lung tension from spontaneous breathing level to the total lung compliance level. FCLE approximates 1 in healthy subjects and in patients with normal lung elastic recoil (LER). LER is lower and the total lung capacity is higher in lung obstructive diseases. Consequently, the total lung compliance could increase and FCLE could grow up to 10 in such cases (for instance, in severe emphysema). This leads to increasing lung activity on overcoming the elastic resistance up to 10 kgf × m / min or higher. Actually, this huge work of breathing is not performed due to the 2nd level of lung mechanical activity that is an active dilation of the large airways on expiration; this mechanism prevents valvular bronchial obstruction.

A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal “expiratory” muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.

Differences in respiratory muscle activity during cycling and walking do not influence dyspnea perception in obese patients with COPD.

In patients with combined obesity and chronic obstructive pulmonary disease (COPD), dyspnea intensity at matched work rates during weight-supported cycling and weight-bearing walking is similar, despite consistent metabolic differences between test modalities. The present study examined the influence of differences in activity of the diaphragm and abdominal muscles during cycling and walking on intensity and quality of dyspnea at matched ventilation in obese patients with COPD. We compared respiratory muscle activity patterns and dyspnea ratings during incremental cycle and treadmill exercise tests, where work rate was matched, in 12 obese (body mass index 36.6 ± 5.4 kg/m(2); mean ± SD) patients with moderate COPD. We used a multipair electrode-balloon catheter to compare electromyography of the diaphragm and esophageal, gastric, and transdiaphragmatic pressures during the two exercise tests. Ventilation, breathing pattern, operating lung volumes, global respiratory effort, and electrical activation of the diaphragm were similar across exercise modalities for a given work rate. The cycling position was associated with greater neuromuscular efficiency of the diaphragm (P < 0.01), greater diaphragm use (P < 0.01) measured by the ventilatory muscle recruitment index, and less expiratory muscle activity compared (P < 0.01) with treadmill walking. However, intensity and quality of dyspnea were similar between exercise modalities. In obese patients with COPD, altered respiratory muscle activity due to body position differences between cycling and walking did not modulate perceived dyspnea when indirect measures of respiratory neural drive were unchanged.

Respiratory-induced venous blood flow effects using flexible retrospective double-gating.

To demonstrate a novel velocity sensitive acquisition and retrospective cardiorespiratory double-gated reconstruction scheme to examine respiratory effect on venous blood flow in healthy volunteers. Radial two dimensional (2D) phase contrast MR is performed at 3 Tesla in the internal jugular vein (IJV) of healthy volunteers (n = 6). Data are retrospectively partitioned based on respiratory waveforms using three schemes: moving average for respiration plateaus, gradient for active respiration, and ten respiratory phases that are cardiac time-averaged. A single 4D flow MR scan is performed in the neck of a healthy volunteer. After gradient operation, blood velocity measurements are made along the IJV length. Percent changes from expiration to inspiration for moving average and gradient techniques are statistically compared with paired t-tests. Percent change increase in summed IJV mean and peak blood flow during active inspiration versus active expiration in 2D was significant (mean flow: 11.5 ± 8.0%, peak flow: 11.9 ± 5.9%, P < 0.01). Smallest cross-sectional area and largest blood velocity are seen during inspiration phases (phase number: area-6.5 ± 3.6, velocity-6.2 ± 3.2). Significant increase in mean velocity along the length of the IJV was observed in 3D, with increasing percent changes more proximal to the chest (mean, 39 ± 30%; range, 0-93%, P = 0.001). With a radial acquisition, this pilot study demonstrates feasibility of simultaneous retrospective cardiorespiratory gating in IJV flow. Greatest differences in flow occur between active respiration phases, increasing in magnitude more proximal to the chest.

Vagal afferent control of abdominal expiratory activity in response to hypoxia and hypercapnia in rats

In the present study, we tested the hypothesis that vagal afferent information modulates the pattern of expiratory response to hypercapnia and hypoxia. Simultaneous recordings of airflow, diaphragmatic (DIA) and oblique abdominal muscle (ABD) activities were performed in anesthetized (urethane, 1.2g/kg), tracheostomized, spontaneously breathing male Wistar rats (290–320g, n=12). The animals were exposed to hypercapnia (7 and 10% CO2 for 5min) and hypoxia (7% O2 for 1min) before and after bilateral vagotomy. We verified that the percentage increase in DIA burst amplitude elicited by hypercapnia and hypoxia episodes was similar between intact and vagotomized rats (P>0.05). In contrast, hypercapnia and hypoxia promoted a marked increase in ABD activity in vagotomized, but not in intact rats (P<0.01). These amplified expiratory motor changes after vagotomy were associated with enhanced expiratory airflow (P<0.01) and augmented tidal volume responses (P<0.01). Our data indicates that, in anesthetized conditions, the removal of peripheral afferent inputs facilitates the processing of active expiration in response to hypercapnia and hypoxia in rats.

The effects of skin-to-skin care on the diaphragmatic electrical activity in preterm infants

BackgroundSkin-to-skin care (SSC) is widely used in neonatal intensive care units due to its positive effects on infant physiology and parent–infant interaction. AimsWe investigated the safety and the effect of SSC on the diaphragm electrical activity (EAdi) in premature infants recovering from respiratory distress syndrome treated on noninvasive neurally adjusted respiratory assist. Study designAn observational cross-over study design was used. The infants were evaluated during SSC and in both prone and supine positions before and after SSC during a 9-hour study period. The EAdi was measured via miniaturized sensors incorporated into a feeding tube. SubjectsSeventeen premature infants with a mean age of 20d (range, 2–43d) were studied. Their mean birth weight was 900g (490–1845g) and mean gestational age at birth 28wk (25–32wk). Outcome measuresUnder each condition, EAdi peak (representing tidal, neural inspiratory effort) and EAdi minimum (representing neural expiratory activity) were numerically quantified. Oxygen saturation, heart rate, and apnea were recorded. ResultsThe mean EAdi minimum values were lower during SSC and prone position. In addition, a tendency towards lower EAdi peak values was found during SSC. There were no differences in the occurrence of apnea between the study phases. ConclusionsSSC is safe and it is not associated with increased neural activity of the diaphragm. On the contrary, low EAdi minimum values were registered reflecting more complete diaphragmatic de-activation between respiratory cycles.

Proportional assist ventilation versus pressure support ventilation in the weaning of patients with acute exacerbation of chronic obstructive pulmonary disease

BackgroundPatients with COPD are frequently hospitalized for acute exacerbations (AECOPD), which may cause respiratory failure and death. Proportional assist ventilation (PAV) is a relatively new mode of ventilator-based, inspiratory support designed to assist spontaneous breathing in patients with intact neural drive. It is a form of synchronized partial ventilatory assistance with peculiar characteristic that ventilator generates pressure in proportion to patient’s instantaneous effort. Pressure support ventilation (PSV) is an attractive weaning mode, however at higher pressure support levels, many patients displayed expiratory muscle activation indicating that the patient is “fighting the ventilator”. ObjectiveTo compare PAV and PSV in the weaning of AECOPD patients. Patients and methodsThe study was conducted on 60 patients admitted to the Department of Critical Care Medicine, at the Alexandria Main University Hospital with the diagnosis of AECOPD. Exclusion criteria included those with severe cardiac or neurological disease, and those managed by non-invasive ventilation. All patients were subjected on admission to complete history taking, complete physical examination and laboratory investigations and were treated according to guidelines of treatment of AECOPD. At the time of weaning patients were randomly categorized into two equal groups; Group A: patients weaned using PAV and Group B: patients weaned using PSV and the two groups were assessed for weaning success, patient–ventilator dys-synchrony, MV days, ICU, and hospital stay. ResultsThe weaning success rate was 90% in group A, and 66.7% in group B. PAV was associated with less patient–ventilator dys-synchrony and was associated with 1.5day reduction in the mean days of mechanical ventilation, 2day reduction in the mean days of ICU stay, and 1.8day reduction in the mean days of hospital stay in comparison to PSV group. ConclusionPAV was associated with less patient–ventilator dys-synchrony and associated with reduction of days of mechanical ventilation, ICU, and hospital stay.

Does expiratory muscle activity influence dynamic hyperinflation and exertional dyspnea in COPD?

Increased expiratory muscle activity is common during exercise in patients with COPD but its role in modulating operating lung volumes and dyspnea during incremental cycle ergometry is currently unknown. We compared gastric (Pga) and esophageal (Pes) pressures, operating lung volumes and qualitative descriptors of dyspnea during exercise in 12 COPD patients and 12 age- and sex-matched healthy controls. Pes- and Pga-derived measures of expiratory muscle activity were significantly (p<0.05) greater in COPD than in health during exercise. End-expiratory lung volume (EELV) increased by 0.8L, independent of increased expiratory muscle activity in COPD. Dynamic function of the diaphragm was not different in health and COPD throughout exercise. In both groups, dyspnea descriptors alluding to increased work and inspiratory difficulty predominated whereas expiratory difficulty was rarely reported, even at the limits of tolerance. In conclusion, increased expiratory muscle activity did not mitigate the rise in EELV, the relatively early respiratory mechanical constraints or the attendant perceived inspiratory difficulty during exercise in COPD.

Short‐term sustained hypoxia induces changes in the coupling of sympathetic and respiratory activities in rats

Individuals experiencing sustained hypoxia (SH) exhibit adjustments in the respiratory and autonomic functions by neural mechanisms not yet elucidated. In the present study we evaluated the central mechanisms underpinning the SH-induced changes in the respiratory pattern and their impact on the sympathetic outflow. Using a decerebrated arterially perfused in situ preparation, we verified that juvenile rats exposed to SH (10% O2) for 24h presented an active expiratory pattern, with increased abdominal, hypoglossal and vagal activities during late-expiration (late-E). SH also enhanced the activity of augmenting-expiratory neurones and depressed the activity of post-inspiratory neurones of the Bötzinger complex (BötC) by mechanisms not related to changes in their intrinsic electrophysiological properties. SH rats exhibited high thoracic sympathetic activity and arterial pressure levels associated with an augmented firing frequency of pre-sympathetic neurones of the rostral ventrolateral medulla (RVLM) during the late-E phase. The antagonism of ionotropic glutamatergic receptors in the BötC/RVLM abolished the late-E bursts in expiratory and sympathetic outputs of SH rats, indicating that glutamatergic inputs to the BötC/RVLM are essential for the changes in the expiratory and sympathetic coupling observed in SH rats. We also observed that the usually silent late-E neurones of the retrotrapezoid nucleus/parafacial respiratory group became active in SH rats, suggesting that this neuronal population may provide the excitatory drive essential to the emergence of active expiration and sympathetic overactivity. We conclude that short-term SH induces the activation of medullary expiratory neurones, which affects the pattern of expiratory motor activity and its coupling with sympathetic activity.

Effects of acute intermittent hypoxia on sympathetic and expiratory activities in rats (872.8)

The exposure to acute intermittent hypoxia (AIH) produces a long‐lasting increase of phrenic and sympathetic activities in anesthetized rats. In the present study we aimed to evaluate the effects of AIH on baseline expiratory motor activity as well as the role of retrotrapezoid nucleus in the AIH‐induced sympathetic and respiratory changes. In the in situ working heart‐brainstem preparations of juvenile rats (n=4), AIH exposure (10 x 5‐7% O2 for 30 s, every 5 min) increased baseline phrenic (Δ: 20±6%), abdominal (Δ: 65±30%) and sympathetic (Δ: 89±48%) nerve activities (P&lt;0.05) that was maintained for at least 60 min after the last hypoxic episode. In conscious adult rats (n=9), AIH evoked an increase in baseline arterial pressure (Δ: 7±2 mmHg), associated with enhanced sympathetic‐ and respiratory‐related variabilities (P&lt;0.05). In adult urethane‐anesthetized rats with intact vagus (n=5), AIH increased baseline arterial pressure (Δ: 9±1 mmHg) and abdominal muscle contraction amplitude (Δ: 412±117%), which were reverted by pharmacological inhibition of retrotrapezoid nucleus (P&lt;0.05). These data indicate that AIH promotes a sustained increase of expiratory activity, in addition to inspiratory and sympathetic activities. Moreover, AIH‐induced sympathetic and expiratory long‐term facilitation may involve, at least in part, the activation of the retrotrapezoid nucleus.Grant Funding Source: Supported by FAPESP (09/54888‐7; 11/20040‐1) and CNPq

Examining the role of inhibition in establishing the three respiratory phases in a horizontal slice (712.14)

Breathing is composed of three phases: inspiration (I), post‐inspiration (E1), and active expiration (E2). Essential for the generation of breathing is the preBtzinger complex (preBtC). Isolated in transverse slices (TS) the preBtC generates predominantly inspiratory activity which can be recorded as population activity. Yet, the preBtC is only one part of a wider respiratory network that is distributed along the rostro‐caudal axis of the ventral respiratory column (VRC) in the ventrolateral medulla of the brainstem. The interactions between this extended respiratory network and how it generates different forms of expiration are not entirely understood. We recently developed a novel horizontal slice (HS) preparation (CD1 mice, p5‐8) that preserves the entire VRC bilaterally while maintaining amenability for intracellular manipulation. Inspiratory population bursts from the HS preBtC are broader compared to the TS and appear to consist of two components. Burst durations in the HS decrease in the presence of 1µM strychnine, and we hypothesize that the increased burst durations reflect the glycine‐dependent partial separation of the I and E1 phases. Moreover, we discovered an additional, yet conditional rhythm rostral to the preBtC that is tightly coupled to the inspiratory rhythm. Based on the location, the phase, and the low spontaneous frequency of the rostral rhythm, we hypothesize that it represents the E2 phase. The rostral rhythm can be stimulated with 4uM norepinephrine or hypoxia and can be tightly coupled to fictive sighs in the HS. The addition of 10µM gabazine synchronizes the two rhythms suggesting that the separation of I and E2 is GABA‐dependent. Thus, the horizontal slice offers a novel approach to examining the role of inhibition in generating expiration.Grant Funding Source: Supported by the NIH

State‐dependent regulation of breathing by the retrotrapezoid nucleus (872.10)

In this study we stimulated the retrotrapezoidal neurons (RTN) by optogenetics in behaving animals to determine ventilatory responses across sleep and wake states. We targeted the rostral RTN region (n=12) with a PRSX8 promoter lentivirus and limited ChannelRhodopsin expression to RTN neurons and noradrenergic A5 neurons. A subset of rats (n=6) also received intraspinal anti‐DBH‐saporin, a catecholaminergic‐specific neurotoxin, to eliminate A5 neurons. We observed no significant differences for the resting or evoked ventilatory behavior after effective lesion. In quiet awake and non‐rapid eye movement (nREM; quiet asleep) states, RTN stimulation increased respiratory frequency and tidal volume, and could entrain respiratory rate between 1.2Hz ‐ 2Hz. We also observed active expiration in the wake state only. The increase in breathing by RTN stimulation was occluded by hypercapnia (6% CO2), but not hypoxia (12% O2). Surprisingly, RTN stimulation in REM (active sleep) failed to increase or pace respiratory rate and only tidal volume was significantly increased. This REM phenomenon draws an intriguing parallel to voluntary breathing (active wake), where homeostatic mechanisms are limited to adjusting the depth of each cortically‐triggered breath.Grant Funding Source: Supported by NIH (HL28785, HL74011)

Coordination of swallow and breathing: in vivo and computational model simulations (1178.12)

Coordination of swallow and breathing is vital for airway protection. However, the central mechanisms for the coordination of these behaviors are not known. We speculated that coupled oscillators could be used to explain swallow‐breathing interactions. In vivo recordings in anesthetized cats (n=6) demonstrate that swallow exhibits respiratory phase preference with 83% during expiration (E), 7% during inspiration (I), and 10% phase transition. A swallow oscillator circuit with two, mutually inhibitory, neuron populations, (A &amp;amp; B) was added to the extant medullary breathing network. The swallow A group excites downstream motoneurons and the swallow B group controls inter‐swallow duration. To loosely couple the oscillators excitatory connections were added: 1) I populations to swallow B, controlling swallow occurrence during E phase; 2) E‐augmenting population to swallow B, increasing the probability of swallow occurrence near the end of E. Additionally, to reduce expiratory activity during swallow, an excitatory connection was added between the swallow A population and an E decrementing population, which in turn suppressed E‐Aug bulbospinal activity. Simulations exhibited repetitive breathing, and swallow occurred during the appropriate breathing phase. We conclude significant features of the swallow‐breathing relationship can be modeled with loosely coupled oscillators. NIH HL89104, HL103415, HL89071, HL109025, HL 111215(K99/R00)Grant Funding Source: NIH HL89104, HL103415, HL89071, HL109025, HL 111215 (K99/R00)

A novel technique of non‐invasive ventilation: Pharyngeal oxygen with nose‐closure and abdominal‐compression—Aid for pediatric flexible bronchoscopy

To evaluate the safety, feasibility and efficacy of a novel non-invasive ventilation (NIV) technique--pharyngeal oxygen with nose-closure and abdominal-compression (PhO2 -NC-AC)--to aid pediatric flexible bronchoscopy (FB). A prospective 1 year study of patients who received FB. A basic PhO2 flow (0.5-1.0 L/kg/min, maximal 5.0 L/min) was routinely applied. Active NIV was initiated when the heart rate dropped <80 beats/min or desaturation was <80% for >10 sec. It was performed as follows: NC 1 sec for inspiration then released, followed by AC 1 sec for active expiration at a rate of 20-30 cycles/min until vital signs returned to acceptable levels for >10 sec. When the patients were stable, supplementary NIV was optionally given. Cardiopulmonary parameters were collected and analyzed. Three hundred thirty-seven FBs, including 188 therapeutic, were conducted in 286 patients with a mean age of 18.3 months (± 14.4, 10 min to 12 years) and a mean body weight of 13.5 kg (± 6.7, 0.5-35 kg). Three hundred thirty-three active NIVs were executed with a mean duration of 87.8 sec (± 40.4, 28-190 sec). A significantly longer FB duration (33.2 ± 16.7 min vs. 7.2 ± 2.8 min, P < 0.001) and a higher application rate of active NIV (1.44/FB vs. 0.42/FB) were noted in the therapeutic compared to the diagnostic group. Vital signs and blood gases (35 cases) improved rapidly and returned to baseline within 3 min. All FBs were safely and successfully completed without significant complications. PhO2 -NC-AC is a simple, safe and effective NIV technique for respiratory support and rescue during various pediatric FB procedures.

Pain assessment scales in nonverbal critically ill adult patients: ventilator-related issues

critical points regarding these scales. First, the CPOT and the BPS do not have a specific item for patients who are in a coma (Glasgow Coma Scale ≤8), with artificial airways (eg, tracheostomy tube), who are breathing spontaneously without receiving mechanical ventilation. Other important concerns are items that evaluate patients’ compliance with ventilators. When patients cough we expect to hear the sound of ventilator alarms, which occurs only if alarms have been adequately set up. Consequently, the evaluation of this item is dependent on the variability of clinical settings and health care professionals. Another element that can make it difficult to recognize a patient “fighting with the ventilator” is the use of ventilation modes based on active expiration valves (eg, BIPAP, Drager; DuoPAP, Hamilton; BiVent, Siemens; Bi-Level, Puritan BennettCovidien). These ventilation modes let the patients breathe spontaneously, without activating the ventilator alarms. The identification of patient-ventilator asynchronies is made by the direct observation of patients and the interpretation of ventilator waveforms. A recent European survey has shown a wide variability in ventilator education provided to ICU nurses. Unfortunately we do not know how many nurses are “comfortable” with ventilator graph interpretation, even if 83% consider waveform analysis education “important” or “very important.” Presently, there is a lack of papers published about this issue. Finally, some clinical conditions, not necessarily related to pain, can determine the activation of ventilator alarms due to patients’ dyssynchronies: hiccup and seizures. These conditions can determine false positive results. We hope that our observations can be helpful to improve these pain assessment tools for critically ill patients. CCN

Chapter 8 - Expiration: Breathing's other face

The evolution of the aspiration pump seen in tetrapod vertebrates from the buccal-pharyngeal force pump seen in air breathing fish and amphibians appears to have first involved the production of active expiration. Active inspiration arose later. This appears to have involved reconfiguration of a parafacial oscillator (now the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN)) to produce active expiration, followed by reconfiguration of a paravagal oscillator (now the preBötC) to produce active inspiration. In the ancestral breathing cycle, inspiration follows expiration, which is in turn followed by glottal closure and breath holding. When both rhythms are expressed, as they are in reptiles and birds, and mammals under conditions of elevated respiratory drive, the pFRG/RTN appears to initiate the respiratory cycle. We propose that the coordinated output of this system is a ventilation cycle characterized by four phases. In reptiles, these consist of active inspiration (I), glottal closure (E1), a pause (an apnea or breath hold) (E2), and an active expiration (E3) that initiates the next cycle. In mammals under resting conditions, active expiration (E3) is suppressed and inspiration (I) is followed by airway constriction and diaphragmatic braking (E1) (rather than glottal closure) and a short pause at end-expiration (E2). As respiratory drive increases in mammals, expiratory muscle activity appears. Frequently, it first appears immediately preceding inspiration (E3) just as it does in reptiles. It can also appear in E1, however, and it is not yet clear what mechanisms underlie when and where in the cycle it appears. This may reflect whether the active expiration is recruited to enhance tidal volume, increase breathing frequency, or both.

Effects of Respiratory Muscle Activity in Stroke Patients after Feedback Breathing Exercise

and decrease involuntary respira -tion, triggering changes inrespiratory adjustment(1)and decrease inmovement of the thoracic wall and inelectric activity directly or indirectly affects pul-monary function. Therefore, respiratory efficiencyand changes inrespiratory mechanism of patientsreflect damage and asymmetry of thoracic wallmovement and muscular paralysis. In order toresolve these problems, chest wall expansion andventilation and pulmonary volume and capacityshould be appropriately maintained(2) and evaluationof functional ability of the lungs through precisemeasurement of pulmonary functions, and diagnosis,prognosis, and degree of a disease may be made toobtain the ground for exercise prescription(3). Therehave been diverse previous studies of exercises toimprove respiratory function: a study of respiratoryfunction through a long term use of positive expira -tory pressure mask and flutter treatment in cysticfibrosis patients(4), a study of respiratory muscleactivity through diaphragmatic respiration exercisein chronic obstructive pulmonary disease(COPD)patients(5), a study of abdominal muscle activitythrough respiratory muscle exercise in quadriplegiapatients(6), and a study of abdominal respiratorymuscle activation in muscle dystrophy patients(7),and a study of expiratory muscle activation throughexpiratory muscle strengthening exercise in multiplesclerosis patients(8).Thus far studies of respiratory exercise have con -cerned respiratory muscle activity, superficial respi-ratory movement largely in patients with respiratory

Neural Mechanisms Underlying Breathing Complexity

Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings.

Specificity in monosynaptic and disynaptic bulbospinal connections to thoracic motoneurones in the rat

The respiratory activity in the intercostal nerves of the rat is unusual, in that motoneurones of both branches of the intercostal nerves, internal and external, are activated during expiration. Here, the pathways involved in that activation were investigated in anaesthetised and in decerebrate rats by cross-correlation and by intracellular spike-triggered averaging from expiratory bulbospinal neurones (EBSNs), with a view to revealing specific connections that could be used in studies of experimental spinal cord injury. Decerebrate preparations, which showed the strongest expiratory activity, were found to be the most suitable for these measurements. Cross-correlations in these preparations showed monosynaptic connections from 16/19 (84%) of EBSNs, but only to internal intercostal nerve motoneurones (24/37, 65% of EBSN/nerve pairs), whereas disynaptic connections were seen for external intercostal nerve motoneurones (4/19, 21% of EBSNs or 7/25, 28% of EBSN/nerve pairs). There was evidence for additional disynaptic connections to internal intercostal nerve motoneurones. Intracellular spike-triggered averaging revealed excitatory postsynaptic potentials, which confirmed these connections. This is believed to be the first report of single descending fibres that participate in two different pathways to two different groups of motoneurones. It is of interest compared with the cat, where only one group of motoneurones is activated during expiration and only one of the pathways has been detected. The specificity of the connections could be valuable in studies of plasticity in pathological situations, but care will be needed in studying connections in such situations, because their strength was found here to be relatively weak.